Estrogen deprivation and estrogen receptor α antagonism decrease DSS colitis in female mice

Area of Science:

• Gastroenterology
• Endocrinology
• Immunology

Background:

• Hormonal contraception is linked to increased inflammatory bowel disease (IBD) risk in females.
• Ovarian hormones, specifically estradiol, and estrogen receptors (ER) are implicated in intestinal inflammation progression.

Purpose of the Study:

• To investigate the effects of estradiol and SERM2 on dextran sulfate sodium-induced colitis in mice.
• To explore the role of estrogen receptor alpha (ERα) signaling in colitis.

Main Methods:

• Utilized a mouse model of dextran sulfate sodium-induced colitis.
• Compared outcomes in mice with intact ovaries versus ovariectomized (OVX) mice.
• Administered estradiol or SERM2 prophylactically.

Main Results:

• Ovariectomized mice showed a threefold reduced colitis score compared to intact mice.
• Estradiol supplementation aggravated colitis in OVX mice, increasing scores to levels seen in intact mice.
• Immune infiltration and inflammatory interleukin gene expression (Il1b, Il6, Il17a) significantly increased with estradiol supplementation in OVX mice.
• SERM2 treatment showed a mild but consistent decrease in inflammation in intact animals.
• Cyclooxygenase-2 induction correlated with serum estradiol levels in colitis mice.

Conclusions:

• Estrogen receptor alpha (ERα) signaling appears to play an exacerbating role in colitis.
• Ovarian hormone effects in colitis are significant and warrant further investigation.
• ER antagonists may hold potential for alleviating intestinal inflammation.